Medicines called poorly water-soluble drugs have very low solubility in water and, thus, exhibit a quite low "bioabsorptivity", namely, rate of absorption of drug in living organisms upon oral administration, and are often accompanied by having a poor "biouptake", that is, a low amount of drug absorbed into the body of living organisms. Therefore, attempts have been proposed for making such poorly water-soluble drugs more soluble in water by converting them into water-soluble salts e.g. sodium salt or hydrochloride salt, prescribing the drug as a water-soluble prodrug and so on. Proposals have been made also from the pharmaceutical point of view, for example, addition of a solubilizing agent, such as a surface active agent, to the drug and the enclusion of the drug particles with cyclodextrin. In a fine crystallographic technology, a micropulverization of the original drug powder and treatment for making the drug powder amorphous were also proposed.
Since however, each of these prior art measures has a preferential group of drugs in which they apply to, no practical measure generally applicable for every drug preparation has yet been proposed. It is the position of the art today, that, in particular, a proposal capable of complying with the demand of improving the biouptake of drug may not result in improving the bioadsorptivity of drug. Among the poorly water-soluble drugs however, there are many which are required to have an immediate medicinal effect, therefore, a demand still remains for pharmaceuticals for oral administration which not only have a biouptake but also a prompt bioabsorptivity.
In these circumstances, it has been proposed to utilize various high molecular weight substances for improving the bioabsorptivity of poorly water-soluble drugs.
With respect to the use of high molecular weight gelatine, Japanese Patent Application Kokai No. 26615/1982 discloses a technique of co-crushing poorly water-soluble drugs with high molecular weight gelatine etc. This technique employs a large amount of gelatine to be added for improving the bioabsorptivity of poorly water-soluble drug and has a shortcoming in that the technique is limited only to the employment of co-crushing.
On the other hand, attempts have been made for the use of chitin or chitosan obtained from the shells of crab and lobster in pharmaceutical applications. Most of the uses of chitin and chitosan have, however, been directed only to a gradual liberation of a pharmaceutical in living organisms and there is still only a few reports of the solubilization of poorly water-soluble drugs.
Japanese Patent Publication No. 28414/1988 discloses a method for improving the bioabsorptivity and the biouptake of a poorly water-soluble drugs selected from the group consisting of antibiotics and antiepileptics, by subjecting the drug to mixing and co-crushing together with chitin and/or chitosan to such an extent that most of the drug is rendered amorphous. This Japanese Patent Publication does not disclose, however, the use of low molecular weight chitosan and the method exhibits problems not only by requiring large amounts of energy consumption and extensive time for the mixing and co-crushing but by also in making the pharmaceutical process complex.
There is, on the other hand, a report as to a technical measure for improving the dissolution rate of kitasamycin by mixing it with various high molecular weight substances by a roller mixer ["Hyomen" 26 (5), 336 (1988)], in which chitosan is employed in a form of a solution of acetic acid salt, the effect of which is lower than that of polyvinylpyrrolidone as seen by a comparison of the data.
An object of the present invention is to solve the problems explained above and to provide a drug composition in which the solubility and the rate of dissolution of various poorly water-soluble drugs are improved.
Another object of the present invention is to provide a drug composition containing one or more poorly water-soluble drugs capable of being prepared in various forms by means of various pharmacological processes of wet and dry systems, co-crushing, spray granulation and so on.